Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA

Piazza, F., Greenberg, S., Savoiardo, M., Gardinetti, M., Chiapparini, L., Raicher, I., et al. (2013). Anti-Aβ autoantibodies in cerebral amyloid angiopathy-related inflammation: Implications for amyloid-modifying therapies. ANNALS OF NEUROLOGY, 73(4), 449-458 [10.1002/ana.23857].

Anti-Aβ autoantibodies in cerebral amyloid angiopathy-related inflammation: Implications for amyloid-modifying therapies

PIAZZA, FABRIZIO
Primo
;
GARDINETTI, MARGHERITA;FERRARESE, CARLO;DI FRANCESCO, JACOPO COSIMO
2013

Abstract

Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA
Articolo in rivista - Articolo scientifico
Amyloid Related Imaging Abnormalities, ARIA, Alzheimer's disease, Cerebral Amyloid Angiopathy-related inflammation, CAA-ri, Cerebral Amyloid Angiopathy, auto-antibodies against Amyloid beta, beta Amyloid
English
449
458
10
Piazza, F., Greenberg, S., Savoiardo, M., Gardinetti, M., Chiapparini, L., Raicher, I., et al. (2013). Anti-Aβ autoantibodies in cerebral amyloid angiopathy-related inflammation: Implications for amyloid-modifying therapies. ANNALS OF NEUROLOGY, 73(4), 449-458 [10.1002/ana.23857].
Piazza, F; Greenberg, S; Savoiardo, M; Gardinetti, M; Chiapparini, L; Raicher, I; Nitrini, R; Sakaguchi, H; Brioschi, M; Billo, G; Colombo, A; Lanzani, F; Piscosquito, G; Carriero, M; Giaccone, G; Tagliavini, F; Ferrarese, C; DI FRANCESCO, J
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/43093
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